IMAGE: RNA for SARS-CoV-2 (pink) and the ACE2 receptor (white) were found in human salivary gland cells, which are outlined in green. view more
Credit: Paola Perez, PhD, Warner Lab, NIDCR
An international team of scientists has found evidence that SARS-CoV-2, the virus that causes COVID-19, affects cells in the mouth. Although the above airways and lungs are known to be the main sites of SARS-CoV-2 infection, there are indications that the virus can invade cells in other parts of the body, such as the digestive system, blood vessels, kidneys and, as a new study shows, the mouth. The ability of the virus to help define several areas of the body may help explain the broad symptoms that COVID-19 patients experience, including oral symptoms such as loss of taste, dry mouth and bloating. In addition, the findings indicate that the mouth may play a role in the transmission of SARS-CoV-2 to the lungs or digestive system through saliva filled with virus from infectious oral cells. . A better understanding of the role of the mouth could inform strategies to reduce viral transmission inside and outside the body. The team was led by researchers at the National Institutes of Health and the University of North Carolina at Chapel Hill.
“As a result of the overall NIH response to the pandemic, researchers at the National Institute of Dental and Craniofacial Research were able to quickly accelerate their knowledge of oral biology and medicine. answer key questions about COVID-19, ”said NIDCR Director Rena D’Souza, DDS, MS, Ph.D. “The power of this approach has been demonstrated by the efforts of this scientific team, which has identified a potential role of the mouth in the disease and transmission of SARS-CoV-2, a discovery that will contribute to vital knowledge. to fight this disease. “
The study, published online March, 25, 2021 in Nature’s cure, led by Blake M. Warner, DDS, Ph.D., MPH, assistant clinical investigator and head of the NIDCR Salivary Disorder Unit, and Kevin M. Byrd, DDS, Ph.D., at the time assistant professor in the Adams School of Dentistry at the University of North Carolina at Chapel Hill. Byrd is now an Anthony R. Volpe research scholar at the Institute of Science and Research of the American Dental Association. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, UK, and Paola Perez, Ph.D., of NIDCR, were co-authors.
Researchers already know that high levels of SARS-CoV-2 can be present in the saliva of people with COVID-19, and studies suggest that saliva testing is almost as reliable as deep nasal swabs. looking for COVID-19. However, scientists do not know exactly where SARS-CoV-2 is in the saliva. In people with COVID-19 who have respiratory symptoms, a virus in saliva may result from nasal drainage or sputum taken from the lungs. But according to Warner, that may not explain how the virus gets into the saliva of people who do not have these respiratory symptoms.
“Based on data from our labs, we suspected that at least some of the virus in saliva could have come from infectious tissues in the mouth itself,” Warner said.
To investigate this potential, the researchers examined oral bones from healthy individuals to identify oral regions susceptible to SARS-CoV-2 infection. In vulnerable cells there is RNA guidance for the production of “entry proteins” that the virus needs to enter cells. RNA for two major enteric proteins – called the ACE2 receptor and the enzyme TMPRSS2 – has been found in specific cells of the salivary glands and nappies that line the oral mucosa. In a small portion of salivary and gingival gland cells (gum), RNA for both ACE2 and TMPRSS2 was expressed in the same cells. This indicated increased vulnerability because the virus is thought to need both enteric proteins to enter cells.
“The sensory levels of the entry factors are similar to those in regions known to be susceptible to SARS-CoV-2 infection, such as the nasal passages lining the nasal passages of the upper airway,” said Warner.
Once the researchers determined that parts of the mouth were susceptible to SARS-CoV-2, they looked for evidence of infection in oral samples from people with COVID-19. In samples collected at NIH from deceased COVID-19 patients, SNA-CoV-2 RNA was present in just over half of the salivary glands studied. In a salivary gland print from one of the dead, as well as from a living person with COVID-19 starvation, the scientists found specific sequences of viral RNA that showed that cells were actively producing semi- new strains of the virus – strengthens the evidence for infection.
Once the team had found evidence of oral infections, they questioned whether these figs could be a source of the virus in saliva. This seemed to be the case. In people with mild or asymptomatic COVID-19, SNA-CoV-2 RNA was found in cells excreted from the mouth into saliva, as well as RNA for the enteric proteins.
To determine if salivary saliva is infected, the researchers exposed saliva from eight people with asymptomatic COVID-19 to healthy cells grown in a basin. Saliva from two of the volunteers caused infection of the healthy cells, raising the possibility that even people without SARS-CoV-2 symptoms could pass infection to others through saliva.
Finally, to investigate the association between oral and viral symptoms in saliva, the saliva team gathered from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who suffered symptoms, those with a virus in their saliva were more likely to report a loss of taste and smell, suggesting that oral infection may be the basis for oral COVID symptoms. -19.
Taken together, the researchers said, the study’s findings suggest that the mouth, through infectious oral cells, plays a greater role in SARS-CoV-2 infection than previously thought.
“When infectious saliva is swallowed or tiny particles of it are ingested, we believe it can carry SARS-CoV-2 further into our throats, lungs, or even the guitars, “Byrd said.
Further research will be needed to confirm the findings in a larger group of people and to determine the exact nature of the oral link to infection and the spread of SARS-CoV-2 within and outside the body.
“By highlighting a potentially undeveloped role for the oral cavity in SARS-CoV-2 disease, our study could open up new study pathways that could lead to a better understanding of course of infection and disease. Such information could inform interventions to combat the virus and relieve COVID-19 oral symptoms, “Warner said.
###
This research was supported by the NIDCR Department of Intramural Research. Support also came from the DK034987 grant from the National Institute of Diabetes and Compensatory Disease (NIDDK) and NIDDK intramural programs, the National Cancer Institute, the NIH Clinical Center, and the National Institute for Allergies and Infectious Diseases. Additional support came from the American Academy of Periodontology / Sunstar Foundation, the American Lung Association, and the Cystic Fibrosis Foundation.
About the National Institute of Dental and Craniofacial Research:
NIDCR is the nation’s leading funder of oral, dental and craniofacial health research.
About the National Institutes of Health (NIH):
NIH, the nation’s medical research agency, comprises 27 Institutes and Centers and is part of the U.S. Department of Health and Human Services. NIH is the leading federal agency that conducts and supports basic, clinical and translational medical examination, and examines the causes, treatments, and cures for both common and rare diseases.